title: Characterizing CEACAM5 interaction with CD8α and CD1d in intestinal homeostasis.
abstract: Normal intestinal epithelial cells (IECs) could act as non-professional antigen-presenting cells, selectively activating CD8(+)-suppressor T cells. An epithelial cell surface glycoprotein, gp180, recognized by monoclonal antibodies B9 and L12 was determined to be critical in this process. Purification and sequence analysis of mAb B9 reactive material revealed amino-acid sequence homology with CEACAM5. We demonstrate that CEACAM5 has properties attributed to gp180, such as CD8α binding and activation of CD8-associated Lck. CEACAM5 is the only CEACAM member interacting with CD1d through the B3 domain. Its N domain (recognized by B9) is required for CD8α binding. Removal of the N-domain glycosylated residues reduces B9 recognition, CD8α binding affinity, and activation of LcK. Therefore, conformational changes in CEACAM5 glycosylation site are critical for its interaction with CD8α. CEACAM5-activated CD8(+) T cells acquire the ability to suppress the proliferation of CD4(+) T cells in vitro in the presence of interleukin (IL)-15 or IL-7. We provide new insights into the role of CEACAM5 and define its specific immunoregulatory properties among the CEACAMs expressed on IECs. We suggest that unique set of interactions between CEACAM5, CD1d, and CD8 render CD1d more class I-like molecule, facilitating antigen presentation and activation of CD8(+)-suppressor regulatory T cells.
authors.affiliation: Immunology Institute, Mount Sinai School of Medicine, New York, New York, USA.
authors.forename: G
authors.initials: G
authors.lastname: Roda
authors.affiliation: Immunology Institute, Mount Sinai School of Medicine, New York, New York, USA.
authors.forename: X
authors.initials: X
authors.lastname: Jianyu
authors.affiliation: Immunology Institute, Mount Sinai School of Medicine, New York, New York, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Park
authors.affiliation: Goodman Cancer Center and Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
authors.forename: L
authors.initials: L
authors.lastname: DeMarte
authors.affiliation: Immunology Institute, Mount Sinai School of Medicine, New York, New York, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Hovhannisyan
authors.affiliation: Immunology Institute, Mount Sinai School of Medicine, New York, New York, USA.
authors.forename: R
authors.initials: R
authors.lastname: Couri
authors.affiliation: Goodman Cancer Center and Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
authors.forename: C P
authors.initials: CP
authors.lastname: Stanners
authors.affiliation: Immunology Institute, Mount Sinai School of Medicine, New York, New York, USA.
authors.forename: G
authors.initials: G
authors.lastname: Yeretssian
authors.affiliation: Immunology Institute, Mount Sinai School of Medicine, New York, New York, USA.
authors.forename: L
authors.initials: L
authors.lastname: Mayer
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D055610:Antigens, CD1d / Q000378:metabolism*; D016827:CD8 Antigens / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002272:Carcinoembryonic Antigen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D058851:GPI-Linked Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006031:Glycosylation; D006706:Homeostasis; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D005810:Multigene Family; D010766:Phosphorylation; D054730:Protein Interaction Domains and Motifs; D016415:Sequence Alignment
chemical_list: D055610:Antigens, CD1d; D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; C527875:CEACAM5 protein, human; D002272:Carcinoembryonic Antigen; D000939:Epitopes; D058851:GPI-Linked Proteins; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)